Lactate up-regulates the expression of PD-L1 in kidney and causes immunosuppression in septic Acute Renal Injury

Abstract

Background: This study aims to explore the mechanism of immunosuppression in septic Acute Renal Injury (AKI) and the role of programmed death-1 (PD-1/PD-L1) pathway in septic AKI. Methods: This study established a septic AKI model by Cecal ligation and puncture (CLP) in C57/B6 mice, ELISA was used to test the level of lactate and creatinine in serum, blood was collected for flow cytometry and kidney samples for Western blot analyses. This study further analyzed the expression of PD-L1 in kidney and the expression of PD-1 in CD4+, CD8+ T cell, and the number of CD3+ T cells to identify apoptosis in T cells in the blood. Results: The CLP sepsis model induced AKI in C57/B6 mice; The expression of PD-1 and PD-L1 were increased in septic AKI mice; PD-1/PD-L1 induced apoptosis in T cells: the number of lymphocytes decreased by 64%, while the number of CD3+ T cells decreased by 27% compared with the sham group; Results also indicated that lactate up-regulates expression of PD-L1 in the kidney. Conclusions: Lactate activated PD-1/PD-L1 pathway can induce immunosuppression by inducing apoptosis in lymphocytes in septic AKI. Moreover, blocking the receptor of lactate or PD-1/PD-L1 might be a new therapy for septic AKI.

Keywords

• Septic AKI
• Lactate
• PD-L1
• PD-1
• T cell
• Immunosuppression